This laboratory is examining the introduction, arrangement and expression of HSV tk gene in cells converted to the tk+ phenotype following exposure to DNA. We are particularly interested in examining the interaction between virus regulatory proteins and specific nucleotide sequences that flank the tk gene. To examine this interaction in detail we are using cloned deletion mutants of the tk gene. These sequences are introduced into cells and integrated into recipient cell CNA or they are allowed to replicate autonomously in COS-7 cells. A regulatory signal is supplied intrans by infecting these cells with an appropriate strain of HSV and then the virus specified tk mRNA and enzyme levels are measured. The long term goal of this study is to elucidate the complex control circuits that interact to regulate the expression of the HSV chromosome.